Reg3A Overexpression Facilitates Hepatic Metastasis by Altering Cell Adhesion in LoVo Colon Cancer Cells.

Reg3A is upregulated in various cancers and considered a potential target for antitumor treatments. However, the effect of Reg3A in metastasis has been elusive. This study aims to disclose the role of Reg3A overexpression in hepatic metastasis of LoVo colon cancer cells. A stable cell line of LoVo cells overexpressing Reg3A (LoVo-luc-Reg3A), labeled with luc reporter gene, was constructed. Cell proliferation, apoptosis, migration, and invasion were determined using MTT, EdU, Hoechst's staining, flow cytometry, and transwell assays, respectively. Hepatic metastasis of LoVo-luc-Reg3A cells was investigated in BALB/c nude mice. Living bioluminescence imaging, histological examination, and mRNA sequencing (mRNA-seq) were performed to assess the metastatic efficiency and gene expression alteration. Reg3A content was determined by Western blotting and Enzyme-Linked Immunosorbent Assay. Cell attachment capacity was determined in the Matrigel culture. Reg3A overexpression did not promote LoVo cell proliferation or apoptosis, but facilitated cell migration and invasion. In the hepatic metastasis model, Reg3A overexpression increased the number of metastatic colonies. The result of mRNA-seq suggested 349 differentially expressed genes (DEGs) by Reg3A upregulation, many of which were related to colon adenocarcinoma tumorigenesis compared to normal colon tissue. Gene ontology enrichment assay indicated that the DEGs are mainly associated with cell adhesion, leukocyte regulation, extracellular matrix (ECM) remodeling, integrin binding, and STAT protein binding. Reg3A overexpression led to an enrichment of Reg3A protein in local tumor tissue of liver metastasis and ECM/intracellular space in ex vivo cultured cells. However, Reg3A concentration in serum and culture medium was relatively low. Reg3A overexpression also resulted in an increased number of cells that attach to Matrigel, which was attenuated by treatments of siRNA-Reg3A and single-chain variable fragment against Reg3A. Endogenous Reg3A overexpression facilitates hepatic metastasis of LoVo colon cancer cells. The prometastatic effect could be contributed by Reg3A enrichment in ECM, which alters the cell adhesion behavior.

[Preventive early intervention strategies for neurodevelopmental disorders of high-risk infants]. / é«˜å±å„¿ç¥žç»å‘è‚²éšœç¢é¢„é˜²æ€§æ—©æœŸå¹²é¢„ç ”ç©¶è¿›å±•.

Neurodevelopmental disorders in children have become a significant global public health concern, impacting child health worldwide. In China, the current intervention model for high-risk infants involves early diagnosis and early treatment. However, in recent years, overseas studies have explored novel preventive early intervention strategies for neurodevelopmental disorders in high-risk infants, achieving promising results. This article provides a comprehensive review of the optimal timing, methods, and intervention models of the preventive early intervention strategies for neurodevelopmental disorders in high-risk infants. The aim is to enhance the awareness and knowledge of healthcare professionals regarding preventive early intervention strategies for neurodevelopmental disorders in high-risk infants, facilitate clinical research and application of such interventions in China, and ultimately reduce the incidence of neurodevelopmental disorders in this high-risk population.

N-glycosylation of disease-specific haptoglobin for the early screening of diabetic retinopathy.

PURPOSE: Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR. EXPERIMENTAL DESIGN: Serum disease-specific haptoglobin-ß (Hp-ß) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non-proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in-gel digestion and enrichment, the intact N-glycopeptides were detected by mass spectrometry. RESULTS: Fucosylation of Hp-ß was significantly increased and sialylation of Hp-ß was significantly decreased in background DR (BDR, an early-stage DR) patients compared with non-diabetic retinopathy patients (p < 0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp-ß was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR. CONCLUSION: Changes in Hp-ß glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.

The performance of a deep learning system in assisting junior ophthalmologists in diagnosing 13 major fundus diseases: a prospective multi-center clinical trial.

Artificial intelligence (AI)-based diagnostic systems have been reported to improve fundus disease screening in previous studies. This multicenter prospective self-controlled clinical trial aims to evaluate the diagnostic performance of a deep learning system (DLS) in assisting junior ophthalmologists in detecting 13 major fundus diseases. A total of 1493 fundus images from 748 patients were prospectively collected from five tertiary hospitals in China. Nine junior ophthalmologists were trained and annotated the images with or without the suggestions proposed by the DLS. The diagnostic performance was evaluated among three groups: DLS-assisted junior ophthalmologist group (test group), junior ophthalmologist group (control group) and DLS group. The diagnostic consistency was 84.9% (95%CI, 83.0% ~ 86.9%), 72.9% (95%CI, 70.3% ~ 75.6%) and 85.5% (95%CI, 83.5% ~ 87.4%) in the test group, control group and DLS group, respectively. With the help of the proposed DLS, the diagnostic consistency of junior ophthalmologists improved by approximately 12% (95% CI, 9.1% ~ 14.9%) with statistical significance (P < 0.001). For the detection of 13 diseases, the test group achieved significant higher sensitivities (72.2% ~ 100.0%) and comparable specificities (90.8% ~ 98.7%) comparing with the control group (sensitivities, 50% ~ 100%; specificities 96.7 ~ 99.8%). The DLS group presented similar performance to the test group in the detection of any fundus abnormality (sensitivity, 95.7%; specificity, 87.2%) and each of the 13 diseases (sensitivity, 83.3% ~ 100.0%; specificity, 89.0 ~ 98.0%). The proposed DLS provided a novel approach for the automatic detection of 13 major fundus diseases with high diagnostic consistency and assisted to improve the performance of junior ophthalmologists, resulting especially in reducing the risk of missed diagnoses. ClinicalTrials.gov NCT04723160.

Tumor-suppressive effect of Reg3A in COAD is mediated by T cell activation in nude mice.

Regenerating family protein 3 A (Reg3A) is highly expressed in a variety of organs and inflammatory tissues, and is closely related to tumorigenesis and cancer progression. However, clinical statistics show that high expression of Reg3A is associated with better prognosis in colorectal cancer (CRC) patients, suggesting a tumor-suppressive effect. The precise action and underlying mechanism of Reg3A in CRC remain controversial. The present study sought to investigate the relationship among Reg3A expression, CRC development, and immune cell alteration in patients using the TCGA, GEPIA, PrognoScan, TIMER and TISIDB databases. Reg3A-overexpressing LoVo cell line (LoVo-Reg3A), a representative of colon adenocarcinoma (COAD), was constructed and the action of Reg3A was assessed in a xenograft nude mouse model. Our bioinformatical analyses revealed that Reg3A upregulation is highly associated with CRC, along with increased frequency of immune cell infiltration. In the xenograft nude mice, Reg3A overexpression offered a tumor-suppressive effect by inhibiting cell proliferation and promoting apoptosis. The result of RNA-seq suggested a positive regulation of leukocytes and an upregulation of T cells in LoVo-Reg3A tumor tissue. CD4+ and CD8+ T cells in tumors, splenic Reg3A-reactive IFN-γ+/CD4+ T cells, and serum TNF-α, IFN-γ and IL-17 were significantly increased by Reg3A overexpression. In the ex vivo co-culture experiment, elevated cytotoxic effect, increased proportion of CD3ε+ T cells, and upregulated expressions of TNF-α, IFN-γ and IL-17 were detected in the PBMCs isolated from LoVo-Reg3A cell-xenografted nude mice. In conclusion, high expression of Reg3A could activate and recruit T cells in COAD leading to the cytotoxic tumor-suppressive effect.

Roxadustat treatment for erythropoiesis-stimulating agent-hyporesponsive anemia in maintenance hemodialysis patients.

OBJECTIVE: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is a prevalent problem affecting hemodialysis (HD) patients. Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. We explored the ability of roxadustat to increase the hemoglobin (Hb) concentration in ESA-hyporesponsive patients undergoing HD and assessed its effect on iron metabolism and inflammation. METHODS: This prospective study included 30 patients with ESA-hyporesponsive anemia who had been undergoing stable dialysis. All patients received roxadustat three times per week for 24 weeks. The primary endpoint was the mean change in Hb from baseline to the average level over weeks 20 to 24. Iron metabolism markers, C-reactive protein, interleukin (IL)-6, and safety were also assessed. RESULTS: At week 24, roxadustat treatment resulted in a 2.5 ± 1.3 g/dL increase in the Hb level. In total, 28 of 30 patients (93.3%) had an Hb level increase of more than 1.0 g/dL from baseline. Seventeen patients (56.7%) met the endpoint, with a mean Hb level of at least 10.0 g/dL. Iron metabolism and IL-6 levels were also improved. CONCLUSIONS: Oral roxadustat is effective for ESA-hyporesponsive anemia in maintenance HD patients and may also improve iron metabolism and IL-6 levels.

New retinal findings in NLRP3-associated autoinflammatory disease.

PURPOSE: To determine whether the rare NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) is associated with retinal changes and to assess the ocular involvement. METHODS: A retrospective cohort study of 20 patients(40 eyes) diagnosed with rare NLRP3-AID at Peking Union Medical College Hospital, from April 2015 to August 2022. Patients underwent a comprehensive ophthalmological examination, including visual acuity, intraocular pressure examination, slit-lamp examination, fundus photography, optical coherence tomography(OCT), and fluorescence angiography (FA). Some patients also underwent optical coherence tomography angiography (OCTA). RESULTS: This study analyzed 40 eyes of 20 patients (11 [55.0%] male; median age, 25.0 years [range, 12-52 years]) and 13 patients (26 eyes, 65%) demonstrated ocular involvement. The most common ophthalmologic manifestation was conjunctivitis (22 eyes, 84.6%), followed by papilledema (14 eyes, 53.8%), retinopathy (10 eyes, 38.5%), optic atrophy (6 eyes, 23.1%), uveitis (4 eyes, 15.4%), reduced pupil light reflex (3 eyes, 11.5%) and cataracts (2 eyes, 7.7%). Ocular involvement was bilateral in 11 patients (55.0%). Five kinds of retinal lesions were seen in 5 patients (10 eyes, 25%) with NLRP3-AID, including peripheral retinal vascular leakage, microaneurysms, macular ischemia, macular epiretinal membrane formation and drusen. CONCLUSIONS: Peripheral retinal vascular leakage, macular ischemia, microaneurysms and drusen are newly identified retinal findings in patients with NLRP3-AID, which suggests the importance of detailed retinal examination in these patients.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

The phenotype and genotype of Chinese adult patients with NLRP3-associated autoinflammatory disease.

OBJECTIVES: NLRP3-associated autoinflammatory disease (NLRP3-AID) is a spectrum of autosomal dominant inherited diseases associated with NLRP3 gene mutations. Reports of Chinese NLRP3-AID cases are limited to date. In the present study, we aim to describe the phenotype and genotype of a cohort of Chinese adult NLRP3-AID patients METHODS: This single-center study included sixteen adult patients diagnosed with NLRP3-AID at Department of Rheumatology, Peking Union Medical College Hospital from April 2015 to September 2021. Whole-exome sequencing using next-generation sequencing was performed in each patient. Clinical data and mutational information were compared with a European cohort. RESULTS: The median age of disease onset was 16 (0-46) years old, and adult-onset was observed in 4 patients (25%). The median time of diagnosis delay was 20 (0-39) years. Five patients (31.3%) had family history of similar symptoms. The most common clinical manifestations were recurrent fever (93.8%), arthralgia/arthritis (81.3%), skin rash (75%), myalgia (62.5%), and central nervous system manifestations (50%). Heterozygous NLRP3 variants detected in these patients were p.T348M (n = 4, 25%), Q703K, V70M, K129R, M116I, P38S, V442I, D303G, G326E, A439V, K829T, L632F and V198M (n = 1, separately). All the variants were missense mutations. CONCLUSIONS: We reported the largest case series of Chinese adult NLRP3-AID patients. The distinct symptoms of NLRP3-AID patients suggest the heterogeneity of disease. P38S, M116I, K129R, V442I and K829T were identified as novel NLRP3 variants. These data expand the clinical phenotypic and genotypic profiles of NLRP3-AID. Key Points • We characterized the clinical and genetic features of sixteen Chinese adult NLRP3-AID patients. • Thirteen NLRP3 gene variants were confirmed in this cohort, and P38S, M116I, K129R, V442I and K829T were identified as novel variants. • Clinical data and mutation information were compared with a European cohort. • We hope these data would expand the phenotypic and genotypic profile of NLRP3-AID and raise the awareness of early diagnosis and accurate treatment among rheumatologists.

Serum disease-specific IgG Fc glycosylation as potential biomarkers for nonproliferative diabetic retinopathy using mass spectrometry.

OBJECTIVE: To explore the potential of serum disease-specific immunoglobulin G (DSIgG) glycosylation as a biomarker for the diagnosis of nonproliferative diabetic retinopathy (NPDR). METHODS: A total of 387 consecutive diabetic patients presenting in an eye clinic without proliferative diabetic retinopathy (DR) were included and divided into those with nondiabetic retinopathy (NDR) (n = 181) and NPDR (n = 206) groups. Serum was collected from all patients for DSIgG separation. The enriched glycopeptides of the tryptic digests of DSIgG were detected using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients were randomly divided into discovery and validation sets (1:1). The differences in glycopeptide ratios between the groups were compared by using Student's t-test or the Mann-Whitney U test. The predictive ability of the model was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: DSIgG1 G1FN/G0FN, G2N/G2, G2FN/G2N and DSIgG2 G1F/G0F, G1FN/G0FN, G2N/G1N, G2S/G2 were significantly different between NDR and NPDR patients (p < 0.05) in both the discovery and validation sets. The prediction model that was built comprising the seven glycopeptide ratios showed good NPDR prediction performance with an AUC of 0.85 in the discovery set and 0.87 in the validation set. CONCLUSION: DSIgG Fc N-glycosylation ratios were associated with NPDR and can be used as potential biomarkers for the early diagnosis of DR.

Comparison of the adjuvant effect of conbercept intravitreal injection at different times before vitrectomy for proliferative diabetic retinopathy.

Purpose: To assess the optimal time of intravitreal conbercept (IVC) treatment prior to pars plana vitrectomy (PPV) in patients with severe proliferative diabetic retinopathy (PDR). Method: This study was exploratory in nature. Forty-eight consecutive patients (48 eyes) with PDR were divided into four groups according to different IVC times (0.5 mg/0.05 mL) before PPV: group A (3 days), group B (7 days), group C (14 days), and group D (non-IVC). Intraoperative and postoperative effectiveness were assessed, and vitreous VEGF concentrations were detected. Result: For intraoperative effectiveness, groups A and D had a higher incidence of intraoperative bleeding than groups B and C (P = 0.041). Furthermore, groups A-C required less surgical time than group D (P < 0.05). For postoperative effectiveness, group B had a significantly higher proportion of visual acuity that improved or remained unchanged than group D (P = 0.014), and groups A-C had lower proportions of postoperative bleeding than group D. The vitreous VEGF concentration of group B (67.04 ± 47.24 pg/mL) was significantly lower than that of group D (178.29 ± 110.50 pg/mL) (P = 0.005). Conclusion: IVC treatment that was administered 7 days preoperatively was associated with better effectiveness and a lower vitreous VEGF concentration than its administration at other time points.

Mendelian Randomization and Transcriptome-Wide Association Analysis Identified Genes That Were Pleiotropically Associated with Intraocular Pressure.

BACKGROUND: Intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. However, the mechanisms underlying the controlling of IOP remain to be elucidated. OBJECTIVE: To prioritize genes that are pleiotropically associated with IOP. METHODS: We adopted a two-sample Mendelian randomization method, named summary-based Mendelian randomization (SMR), to examine the pleiotropic effect of gene expression on IOP. The SMR analyses were based on summarized data from a genome-wide association study (GWAS) on IOP. We conducted separate SMR analyses using Genotype-Tissue Expression (GTEx) and Consortium for the Architecture of Gene Expression (CAGE) expression quantitative trait loci (eQTL) data. Additionally, we performed a transcriptome-wide association study (TWAS) to identify genes whose cis-regulated expression levels were associated with IOP. RESULTS: We identified 19 and 25 genes showing pleiotropic association with IOP using the GTEx and CAGE eQTL data, respectively. RP11-259G18.3 (PSMR = 2.66 × 10-6), KANSL1-AS1 (PSMR = 2.78 × 10-6), and RP11-259G18.2 (PSMR = 2.91 × 10-6) were the top three genes using the GTEx eQTL data. LRRC37A4 (PSMR = 1.19 × 10-5), MGC57346 (PSMR = 1.19 × 10-5), and RNF167 (PSMR = 1.53 × 10-5) were the top three genes using the CAGE eQTL data. Most of the identified genes were found in or near the 17q21.31 genomic region. Additionally, our TWAS analysis identified 18 significant genes whose expression was associated with IOP. Of these, 12 and 4 were also identified by the SMR analysis using the GTEx and CAGE eQTL data, respectively. CONCLUSIONS: Our findings suggest that the 17q21.31 genomic region may play a critical role in the regulation of IOP.

Development of Diagnostic Recommendations for Vitreoretinal Lymphoma.

PURPOSE: To develop diagnostic recommendations for diffuse large B-cell vitreoretinal lymphoma (VRL) in Chinese patients. METHODS: Retrospective observational case series. Seventy-three eyes of 40 VRL patients and 8 control patients were analyzed. Eighteen patients from Beijing Tongren Hospital and 46 patients from literature were involved as validations. RESULTS: Diagnostic methods included (1) typical clinical manifestations; (2) vitreous cytology; (3) immunohistochemical examination of vitreous or choroid/retina; (4) aqueous humor or vitreous cytokine; (5) vitreous cell gene rearrangement; (6) vitreous flow cytometry. If patients meet (1)+(2)+(3), or if they meet (1), and two of (4), (5), (6) are positive, they can be diagnosed as VRL. The sensitivity and specificity values for accurate diagnosis were 0.975 and 1.00. One hundred percent eyes from Beijing Tongren Hospital and 92.7% eyes from literature can be diagnosed. CONCLUSION: We developed diagnostic recommendations for diffuse large B-cell VRL through vitreous cytology combined with multiple auxiliary examinations.

Early onset drusen and RPE dysfunction in a patient with NLRP3-AID.

Retinal pigment epithelium (RPE) dysfunction, manifested as drusen formation and RPE mottling, is a characteristic lesion of aging. The mechanism of RPE dysfunction remains unknown. Previous animal studies have proven that the activation of NLRP3 inflammasome in RPE leads to apoptosis and pyroptosis, which may play a very important role in the development of age-related macular degeneration (AMD). However, there is a lack of clinical evidence to support the above hypothesis. Herein, we report a 38-year-old Chinese Han woman who had NLRP3-associated autoinflammatory disease (NLRP3-AID) with widely scattered drusen at the posterior pole in both eyes. NLRP3-AID is a rare disease caused by mutations of the NLRP3 gene, leading to NLRP3 inflammasome activation. This report of early-onset drusen provides clinical evidence that the NLRP3 inflammasome might contribute to the occurrence of RPE dysfunction and is a potential cause of age-related macular degeneration (AMD).

Analysis of risk factors for neonatal preterm birth and construction of nomogram prediction model / 中国热带医学

@#Abstract: Objective To analyze the risk factors for neonatal preterm birth in 12 hospitals in Yunnan Province from 2016 to 2017, and to establish a nomogram prediction model for neonatal preterm birth, providing scientific evidence for the prevention of preterm birth. Methods A total of 20 445 pregnant women who gave birth in 12 hospitals in Yunnan Province from 2016 to 2017 were collected and grouped into a preterm group (n=1 186) and a full-term group (n=19 259) according to whether they had a premature delivery. The general information questionnaire of pregnant women designed by the research team was applied to understand the basic conditions and pregnancy information of the two groups, and the risk factors of preterm birth were determined by logistic regression analysis, R software was applied to draw a nomogram prediction model of neonatal preterm birth, and its predictive performance was tested. Results There were significant differences in the proportions of twins and above (9.11% vs 7.10%), pregnancy-induced hypertension (21.67% vs 18.57%), gestational diabetes mellitus (18.21% vs 15.90%), anemia (24.28% vs 20.70%), premature rupture of membranes (11.64% vs 9.76%), and abnormal placenta (7.08% vs 5.51%) between the preterm group and the full-term group (χ2=6.731, 7.055, 4.441, 8.691, 4.437, 5.232, all P<0.05); the logistic regression analysis showed that the risk factors for neonatal preterm birth were twins and above (OR=2.378), pregnancy-induced hypertension (OR=2.039), gestational diabetes mellitus (OR=1.824), anemia (OR=1.825), and premature rupture of membranes (OR=2.313) (all P<0.05); the discrimination (area under the curve was 0.794, 95%CI=0.738-0.850) and precision (goodness of fit HL test, χ2=8.864, P=0.312) of the nomogram model constructed to predict the occurrence of neonatal preterm birth were both good. Conclusions The nomogram model for preterm birth constructed based on 5 factors including number of fetuses, pregnancy-induced hypertension, gestational diabetes mellitus, anemia and premature rupture of membranes can predict the occurrence of neonatal preterm birth well, thus providing reference for the prevention of neonatal preterm birth.

Global trends and frontiers of research on pathologic myopia since the millennium: A bibliometric analysis.

Background and purpose: Pathologic myopia (PM) is an international public health issue. This study aimed to analyze PM research trends by reporting on publication trends since 2000 and identifying influential journals, countries, authors, and keywords involved in PM. Methods: A bibliometric analysis was performed to evaluate global production and development trends in PM since 2000 and the keywords associated with PM. Results: A total of 1,435 publications were retrieved. PM has become a fascinating topic (with relative research interest ranging from 0.0018% in 2000 to 0.0044% in 2021) and a global public health issue. The top three countries with the highest number of publications were China, the USA, and Japan. The journals, authors, and institutions that published the most relevant literature came from these three countries. China exhibited the most rapid increase in the number of publications (from 0 in 2000 to 69 in 2021). Retina published the most papers on PM. Kyoko Ohno-Matsui and Tokyo Medical and Dental University contributed the most publications among authors and institutions, respectively. Based on keyword analysis, previous research emphasized myopic choroidal neovascularization and treatment, while recent hotspots include PM changes based on multimodal imaging, treatment, and pathogenesis. Keyword analysis also revealed that deep learning was the latest hotspot and has been used for the detection of PM. Conclusion: Our results can help researchers understand the current status and future trends of PM. China, the USA, and Japan have the greatest influence, based on the number of publications, top journals, authors, and institutions. Current research on PM highlights the pathogenesis and application of novel technologies, including multimodal imaging and artificial intelligence.

Publication trends of artificial intelligence in retina in 10 years: Where do we stand?

Purpose: Artificial intelligence (AI) has been applied in the field of retina. The purpose of this study was to analyze the study trends within AI in retina by reporting on publication trends, to identify journals, countries, authors, international collaborations, and keywords involved in AI in retina. Materials and methods: A cross-sectional study. Bibliometric methods were used to evaluate global production and development trends in AI in retina since 2012 using Web of Science Core Collection. Results: A total of 599 publications were retrieved ultimately. We found that AI in retina is a very attractive topic in scientific and medical community. No journal was found to specialize in AI in retina. The USA, China, and India were the three most productive countries. Authors from Austria, Singapore, and England also had worldwide academic influence. China has shown the greatest rapid increase in publication numbers. International collaboration could increase influence in this field. Keywords revealed that diabetic retinopathy, optical coherence tomography on multiple diseases, algorithm were three popular topics in the field. Most of top journals and top publication on AI in retina were mainly focused on engineering and computing, rather than medicine. Conclusion: These results helped clarify the current status and future trends in researches of AI in retina. This study may be useful for clinicians and scientists to have a general overview of this field, and better understand the main actors in this field (including authors, journals, and countries). Researches are supposed to focus on more retinal diseases, multiple modal imaging, and performance of AI models in real-world clinical application. Collaboration among countries and institutions is common in current research of AI in retina.

Circ_0000181 regulates miR-667-5p/NLRC4 axis to promote pyroptosis progression in diabetic nephropathy.

Our previous research demonstrated that NOD-like receptor family CARD domain-containing protein 4 (NLRC4) inflammasome was overexpressed in renal tissues of patients with diabetic nephropathy (DN). This study further investigated the effect of circRNAs-miRNAs interaction on NLRC4 and their potential mechanisms. DN mice models were first established using STZ. Then, pyroptosis related marker expression was detected using qPCR, western blot (WB), and immunohistochemistry analysis. After that, differentially expressed circRNAs, miRNAs, and mRNAs were investigated using next-generation sequencing. Additionally, the function and potential mechanism of circ_0000181 and miR-667-5p on pyroptosis were measured in vitro DN cell model using MTS, WB, and Enzyme-linked immunosorbent assay. There was an apparent elevation of NLRC4, Caspase1, IL-1ß, and IL-18 levels in DN mice. The next-generation sequencing results revealed that there were 947 circRNAs and 390 miRNAs significantly different between the DN and sham kidney tissue, of which circ_0000181 and miR-667-5p had potential targeting effects with NLRC4. Dual-luciferase and functional rescue experiments demonstrated that circ_0000181 promoted NLRC4 inflammasome activation via competitive sponge of miR-667-5p, promoted the release of IL-1ß and IL-18, and caused pyroptosis. Altogether, circ_0000181 regulates miR-667-5p/NLRC4 axis to promote pyroptosis progression in DN.

An Artificial-Intelligence-Based Automated Grading and Lesions Segmentation System for Myopic Maculopathy Based on Color Fundus Photographs.

Purpose: To develop deep learning models based on color fundus photographs that can automatically grade myopic maculopathy, diagnose pathologic myopia, and identify and segment myopia-related lesions. Methods: Photographs were graded and annotated by four ophthalmologists and were then divided into a high-consistency subgroup or a low-consistency subgroup according to the consistency between the results of the graders. ResNet-50 network was used to develop the classification model, and DeepLabv3+ network was used to develop the segmentation model for lesion identification. The two models were then combined to develop the classification-and-segmentation-based co-decision model. Results: This study included 1395 color fundus photographs from 895 patients. The grading accuracy of the co-decision model was 0.9370, and the quadratic-weighted κ coefficient was 0.9651; the co-decision model achieved an area under the receiver operating characteristic curve of 0.9980 in diagnosing pathologic myopia. The photograph-level F1 values of the segmentation model identifying optic disc, peripapillary atrophy, diffuse atrophy, patchy atrophy, and macular atrophy were all >0.95; the pixel-level F1 values for segmenting optic disc and peripapillary atrophy were both >0.9; the pixel-level F1 values for segmenting diffuse atrophy, patchy atrophy, and macular atrophy were all >0.8; and the photograph-level recall/sensitivity for detecting lacquer cracks was 0.9230. Conclusions: The models could accurately and automatically grade myopic maculopathy, diagnose pathologic myopia, and identify and monitor progression of the lesions. Translational Relevance: The models can potentially help with the diagnosis, screening, and follow-up for pathologic myopic in clinical practice.

Learning Two-Stream CNN for Multi-Modal Age-Related Macular Degeneration Categorization.

This paper tackles automated categorization of Age-related Macular Degeneration (AMD), a common macular disease among people over 50. Previous research efforts mainly focus on AMD categorization with a single-modal input, let it be a color fundus photograph (CFP) or an OCT B-scan image. By contrast, we consider AMD categorization given a multi-modal input, a direction that is clinically meaningful yet mostly unexplored. Contrary to the prior art that takes a traditional approach of feature extraction plus classifier training that cannot be jointly optimized, we opt for end-to-end multi-modal Convolutional Neural Networks (MM-CNN). Our MM-CNN is instantiated by a two-stream CNN, with spatially-invariant fusion to combine information from the CFP and OCT streams. In order to visually interpret the contribution of the individual modalities to the final prediction, we extend the class activation mapping (CAM) technique to the multi-modal scenario. For effective training of MM-CNN, we develop two data augmentation methods. One is GAN-based CFP/OCT image synthesis, with our novel use of CAMs as conditional input of a high-resolution image-to-image translation GAN. The other method is Loose Pairing, which pairs a CFP image and an OCT image on the basis of their classes instead of eye identities. Experiments on a clinical dataset consisting of 1,094 CFP images and 1,289 OCT images acquired from 1,093 distinct eyes show that the proposed solution obtains better F1 and Accuracy than multiple baselines for multi-modal AMD categorization. Code and data are available at https://github.com/li-xirong/mmc-amd.